The role of the cyclic nucleotides adenosine 3'5' monophosphate and guanosine 3'5' monophosphate in synaptic transmission is under study using cultured cells of neural origin. The topics of interest during the current year have been the following: 1) The receptor-mediated inhibition of adenylate cyclase activity by alpha-adrenergic agents in neuroblastoma x glioma hybrid cells: 2) Demonstration of a compensatory induction of adenylate cyclase activity in cells treated for one or more days with alpha-adrenergic agents, as had been previously demonstrated by others for opiates, and study of the mechanism of this compensatory induction; 3) The effect of opiates and alpha-adrenergic agents on guanosine 3'5' monophosphate levels in the hybrid cells; 4) Search for a cultured-cell system which synthesizes a peptide with opiate-like properties.